Evaluation of the Association between FGFR2 Gene Polymorphisms and Breast Cancer Risk in the Bangladeshi Population
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Sample Preparation
2.3. Genotyping
2.4. Statistical Analysis
3. Results
3.1. Demographic and Clinicopathological Characteristics
3.2. Association of FGFR2 Polymorphisms with Breast Cancer
3.3. Association of FGFR2 Polymorphisms with Clinicopathological Variables
3.4. Analysis of In Silico Gene Expression
3.5. Genotype-Based FGFR2 mRNA Expression
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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SNP | Primer Sequences | PCR Conditions | No. of Cycles | Size of PCR Products | RE | Digestion Conditions | Digested Fragment Size (bp) |
---|---|---|---|---|---|---|---|
rs1219648A > G | FP: 5′-ACGCCTATTTTACTTGACACGC-3′ RP: 5′-GCTGGACAGGTCATTGTGGTG-3′ | 94 °C for 5 min 94 °C for 30 s 53 °C for 30 s 72 °C for 30 s 72 °C for 10 min 4 °C for ∞ | 35 | 230 bp | HinP1I | Incubation at 37 °C, 12 h. | NH: 230 (AA) HE: 230, 211, 19 (AG) MH: 211, 19 (GG) |
rs2420946 C > T | FP: 5′-TTGGTGGAAGAGTCAGAAGA-3′ RP: 5′-GTGGAAAGGGACGAAGTT-3′ | 94 °C for 3 min 94 °C for 30 s 53 °C for 30 s 72 °C for 45 s 72 °C for 5 min 4 °C for ∞ | 35 | 429 bp | HinP1I | Incubation at 37 °C, 12 h. | NH: 107, 322 (CC) HE: 107, 322, 429 (CT) MH: 429 (TT) |
rs2981582 C > T | F: 5′-CCCTTTGGAGACAACGTGAGCC-3′ R: 5′-CAGGCACCAGGTGGACTCTGC-3′ | 94 °C for 3 min 94 °C for 30 s 63 °C for 30 s 72 °C for 30 s 70 °C for 5 min 4 °C for ∞ | 35 | 176 bp | HinP1I | Incubation at 37 °C, 12 h. | NH: 22,154 (CC) HE: 22, 154, 176 (CT) MH: 176 (TT) |
Parameters | Cases (226) | Controls (220) | p-Value |
---|---|---|---|
Age (Years) | 42.89 (10.20) | 41.41 (9.55) | 0.114 |
≤35 | 69 (30.53) | 85 (38.64) | 0.072 |
>35 | 157 (69.47) | 135 (61.36) | |
Marital Status | |||
Married | 220 (97.35) | 208 (94.55) | 0.142 |
Unmarried | 6 (2.65) | 12 (4.55) | |
BMI | |||
Underweight (<18.5) | 15 (6.64) | 12 (5.45) | 0.850 |
Normal (18.50–24.9) | 77 (34.07) | 83 (37.73) | |
Overweight (25–29.9) | 65 (28.76) | 60(27.27) | |
Obese (>29.9) | 69 (30.51) | 65 (29.55) | |
Family History of Breast Cancer | |||
Yes | 28 (12.39 | 15 (6.82) | 0.049 |
No | 198 (87.61) | 205 (93.18) | |
Smoking | |||
Never | 223 (98.67) | 218 (99.09) | 0.677 |
Ever | 3 (1.33) | 2 (0.91) | |
Age at Menarche | |||
≤13 | 161 (71.24) | 158 (71.82) | |
>13 | 65 (28.76) | 62 (28.18) | 0.892 |
Menopausal Status | |||
Continue | 149 (65.93) | 159 (72.27) | 0.148 |
Stop | 77 (34.07) | 61 (27.73) | |
History of OCP | |||
Yes | 167 (73.89) | 167(75.91) | 0.624 |
No | 59 (26.11) | 53 (24.09) | |
Alcoholism | |||
Yes | 1 (0.44) | 0 (0.00) | - |
No | 225 (99.56) | 220 (100) | |
Cases’ Clinicopathological Characteristics | |||
Estrogen Receptor Status | Grade of cancer | ||
ER (+) | 88 (38.94) | Grade 1 | 62 (27.43) |
ER (-) | 138 (61.06) | Grade 2 | 131 (57.96) |
Progesterone Receptor Status | Grade 3 | 33 (14.60) | |
PR (+) | 86 (38.05) | Tumor size | |
PR (-) | 140 (61.95) | T0 | 4 (1.77) |
HER2/neu Status | T1 | 53 (23.45) | |
HER2 (+) | 60 (26.55) | T2 | 94 (41.59) |
HER2 (-) | 166 (73.45) | T3 | 34 (15.04) |
Histological Type of Cancer | T4 | 41 (18.14) | |
Infiltrating Ductal Carcinoma | 83 (36.73) | Lymph Node Status | |
Invasive Ductal Carcinoma | 129 (57.08) | Negative (-) | 81 (35.84) |
Others | 14 (6.19) | Positive (+) | 145 (64.16) |
Nodal Status | Distant Metastasis | ||
N0 | 81 (25.84) | Mx | 170 (75.22) |
N1 | 100 (44.25) | M0 | 51 (22.57) |
N2 | 36 (15.93) | M1 | 5 (2.21) |
N3 | 9 (3.98) |
SNP ID | Model | Genotype/ Allele | Case (%) | Control (%) | HWE | Association Analysis | |
---|---|---|---|---|---|---|---|
aOR (95% Cl) | p-Value | ||||||
rs1219648 | AA | 84 (37.17) | 132 (60.00) | 0.054 | 1 | ||
Additive model 1 (AG vs. AA) | AG | 100 (44.25) | 70 (31.82) | 2.87 (1.76–3.69) | <0.0001 | ||
Additive model 2 (GG vs. AA) | GG | 42 (18.58) | 18 (8.18) | 5.62 (2.52–12.54) | <0.0001 | ||
Dominant model (AG + GG vs. AA) | AA | 84 (37.17) | 132 (60.00) | 1 | |||
AG + GG | 142 (62.83) | 88 (40.00) | 2.87 (1.76–4.69) | <0.0001 | |||
Recessive model (GG vs. AA + AG) | AA + AG | 184 (81.42) | 202 (91.82) | 1 | |||
GG | 42 (18.58) | 18(8.18) | 4.04 (190–8.59) | <0.0001 | |||
Overdominant model (AG vs. AA + GG) | AA + GG | 126 (55.75) | 150 (68.18) | 1 | |||
AG | 100 (44.25) | 70 (31.82) | 1.51 (0.93–2.46) | 0.095 | |||
Allele | A | 268 (59.29) | 334 (75.91) | 1 | |||
G | 184 (40.71) | 106 (24.09) | 2.16 (1.62–2.89) | <0.0001 | |||
rs2420946 | CC | 82 (36.28) | 70 (31.82) | 0.117 | 1 | ||
Additive model 1 (CT vs. CC) | CT | 108 (47.79) | 118 (53.64) | 0.65 (0.38–1.11) | 0.112 | ||
Additive model 2 (TT vs. CC) | TT | 36 (15.93) | 32 (14.55) | 1.30 (0.61–2.76) | 0.499 | ||
Dominant model (CT + TT vs. CC) | CC | 82 (36.28) | 70 (31.82) | 1 | |||
CT + TT | 144 (63.72) | 150 (68.18) | 0.77 (0.47–1.26) | 0.302 | |||
Recessive model (TT vs. CC + CT) | CC + CT | 190 (84.07) | 188 (85.45) | 1 | |||
TT | 36 (15.93) | 32 (14.55) | 1.57 (0.82–3.0) | 0.173 | |||
Overdominant model (CT vs. CC + TT) | CC + TT | 118 (52.21) | 102 (46.36) | 1 | |||
CT | 108 (47.79) | 118 (53.64) | 0.62 (0.39–1.0) | 0.048 | |||
Allele | C | 272 (60.18) | 258 (58.64) | 1 | |||
T | 180 (39.82) | 182 (41.36) | 0.94 (0.72–1.23) | 0.640 | |||
rs2981582 | CC | 78 (34.51) | 90 (40.91) | 1 | |||
Additive model 1 (CT vs. CC) | CT | 98 (43.36) | 102 (46.36) | 0.914 | 0.92 (0.54–1.57) | 0.087 | |
Additive model 2 (TT vs. CC) | TT | 50 (22.12) | 28 (12.73) | 2.60 (1.25–5.37) | 0.010 | ||
Dominant model (CT + TT vs. CC) | CC | 78 (34.51) | 90 (40.91) | 1 | |||
CT + TT | 148 (65.49) | 130 (59.09) | 1.23 (0.76–1.99) | 0.408 | |||
Recessive model (TT vs. CC + CT) | CC + CT | 176 (77.88) | 192 (87.27) | 1 | |||
TT | 50 (22.12) | 28 (12.73) | 2.47 (1.13–4.69) | 0.006 | |||
Overdominant model (CT vs. CC + TT) | CC + TT | 128 (56.64) | 172 (53.64) | 1 | |||
CT | 98 (43.36) | 102 (46.36) | 0.72 (0.45–1.16) | 0.174 | |||
Allele | C | 254 (56.19) | 282 (64.09) | 1 | |||
T | 198 (43.81) | 158 (35.90) | 1.39 (1.06–1.82) | 0.016 | |||
Haplotype | Cases | Controls | χ2 | OR (95% CI) | p-Value | ||
rs1219648, rs2420946, and rs2981582 | ACC | 0.481 | 0.510 | 0.720 | 0.91 (0.70–1.19) | 0.502 | |
GTT | 0.324 | 0.158 | 33.43 | 2.57 (1.86–3.55) | <0.0001 | ||
ATT | 0.029 | 0.144 | 37.69 | 0.18 (0.10–0.33) | <0.0001 | ||
ACT | 0.076 | 0.056 | 1.49 | 1.37 (0.80–2.34) | 0.248 | ||
GTC | 0.038 | 0.062 | 2.54 | 0.61 (0.33–1.13) | 0.115 | ||
GCC | 0.036 | 0.020 | 1.96 | 1.78 (0.78–4.08) | 0.171 | ||
ATC | 0.006 | 0.049 | 15.44 | 0.13 (0.04–0.43) | 0.0009 |
Variables | Total | rs1219648 | OR (95% CI) | p-Value | rs2420946 | OR (95% CI) | p-Value | rs2981582 | OR (95% CI) | p-Value | |||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
AG + GG | AA | CT + TT | CC | CT + TT | CC | ||||||||
Age | |||||||||||||
≤35 | 68 | 42 | 26 | 1 | 41 | 27 | 1 | 48 | 20 | 1 | |||
>35 | 158 | 100 | 58 | 1.07 (0.59–1.92) | 0.828 | 103 | 55 | 1.23 (0.69–2.22) | 0.483 | 100 | 58 | 0.72 (0.39–1.33) | 0.291 |
BMI | |||||||||||||
Underweight (<18.5) | 15 | 9 | 6 | 0.91 (0.29–2.81) | 0.865 | 10 | 5 | 0.85 (0.26–2.77) | 0.791 | 7 | 8 | 0.45 (0.15–1.37) | 0.157 |
Normal (18.50–24.9) | 77 | 48 | 29 | 1 | 54 | 23 | 1 | 51 | 26 | 1 | |||
Overweight (25.00–29.9) | 65 | 32 | 33 | 0.59 (0.30–1.15) | 0.118 | 33 | 32 | 0.44 (0.22–0.87) | 0.019 | 37 | 28 | 0.67 (0.34–1.33) | 0.256 |
Obese (>30) | 69 | 53 | 16 | 2.00 (0.97–4.13) | 0.061 | 47 | 22 | 0.91 (0.45–1.84) | 0.793 | 53 | 16 | 1.69 (0.81–3.51) | 0.161 |
Estrogen Receptor Status | |||||||||||||
ER (−) | 138 | 82 | 56 | 1 | 86 | 52 | 1 | 96 | 42 | 1 | |||
ER (+) | 88 | 60 | 28 | 1.46 (0.83–2.57) | 0.185 | 58 | 30 | 1.17 (0.67–2.05) | 0.584 | 52 | 36 | 0.63 (0.36–1.10) | 0.107 |
Progesterone Receptor Status | |||||||||||||
PR (−) | 140 | 84 | 56 | 1 | 86 | 54 | 1 | 96 | 42 | 1 | |||
PR (+) | 86 | 58 | 28 | 1.38 (0.79–2.43) | 0.262 | 58 | 28 | 1.30 (0.74–2.29) | 0.362 | 52 | 36 | 0.63 (0.36–1.10) | 0.107 |
HER2/neu Receptor Status | |||||||||||||
HER2 (-) | 166 | 97 | 69 | 1 | 110 | 56 | 1 | 111 | 55 | 1 | |||
HER2 (+) | 60 | 45 | 15 | 2.13 (1.10–4.13) | 0.025 | 34 | 26 | 0.67 (0.36–1.22) | 0.186 | 37 | 23 | 0.80 (0.43–1.47) | 0.468 |
Histologic Type of Cancer | |||||||||||||
Infiltrating Ductal Carcinoma | 83 | 54 | 29 | 1 | 49 | 34 | 1 | 57 | 26 | 1 | |||
Invasive Ductal Carcinoma | 129 | 78 | 51 | 0.82 (0.46–1.46) | 0.501 | 88 | 41 | 1.49 (0.84–2.64) | 0.173 | 83 | 46 | 0.82 (0.46–1.48) | 0.516 |
Others | 14 | 10 | 4 | 1.34 (0.39–4.66) | 0.643 | 7 | 7 | 0.69 (0.22–2.16) | 0.528 | 8 | 6 | 0.61 (0.19–1.93) | 0.399 |
Grade of Cancer | |||||||||||||
Grade 1 | 62 | 48 | 14 | 1 | 43 | 19 | 1 | 43 | 19 | 1 | |||
Grade 2 | 131 | 74 | 57 | 0.38 (0.19–0.75) | 0.006 | 80 | 51 | 0.69 (0.36–1.32) | 0.265 | 83 | 48 | 0.76 (0.40–1.46) | 0.415 |
Grade 3 | 33 | 20 | 13 | 0.45 (0.18–1.12) | 0.087 | 21 | 12 | 0.77 (0.32–1.89) | 0.572 | 22 | 11 | 0.88 (0.36–2.18) | 0.789 |
Tumor Size | |||||||||||||
To | 4 | 3 | 1 | 1 | 3 | 1 | 1 | 2 | 2 | 1 | |||
T1 | 53 | 36 | 17 | 0.71 (0.07–7.30) | 0.770 | 30 | 23 | 0.43 (0.04–4.46) | 0.483 | 35 | 18 | 1.94 (0.25–14.97) | 0.523 |
T2 | 94 | 60 | 36 | 0.56 (0.06–5.54) | 0.617 | 61 | 33 | 0.62 (0.06–6.16) | 0.680 | 58 | 36 | 1.61 (0.22–11.95) | 0.641 |
T3 | 34 | 18 | 16 | 0.38 (0.04–3.98) | 0.416 | 22 | 12 | 0.61 (0.08–6.54) | 0.684 | 25 | 9 | 2.78 (0.34–22.75) | 0.341 |
T4 | 41 | 27 | 14 | 0.64 (0.06–6.76) | 0.713 | 28 | 13 | 0.72 (0.07–7.58) | 0.783 | 28 | 13 | 2.15 (0.27–17.03) | 0.467 |
Lymph Node Status | |||||||||||||
Negative (-) | 81 | 58 | 23 | 1 | 51 | 30 | 1 | 63 | 18 | 1 | |||
Positive (+) | 145 | 84 | 61 | 0.55 (0.30–0.98) | 0.043 | 93 | 52 | 1.05 (0.60–1.85) | 0.860 | 85 | 60 | 0.40 (0.22–0.75) | 0.004 |
Nodal Status | |||||||||||||
No | 81 | 48 | 33 | 1 | 42 | 39 | 1 | 53 | 28 | 1 | |||
N1 | 100 | 68 | 32 | 1.46 (0.79–2.69) | 0.224 | 74 | 26 | 2.64 (1.42–4.93) | 0.002 | 63 | 37 | 0.90 (0.49–1.66) | 0.735 |
N2 | 36 | 21 | 15 | 0.96 (0.43–2.14) | 0.925 | 23 | 13 | 1.64 (0.73–3.68) | 0.228 | 26 | 10 | 1.37 (0.58–3.25) | 0.470 |
N3 | 9 | 5 | 4 | 0.86 (0.21–3.44) | 0.831 | 5 | 4 | 1.16 (0.29–4.64) | 0.833 | 6 | 3 | 1.06 (0.25–4.55) | 0.941 |
Distant Metastasis | |||||||||||||
Mx | 170 | 113 | 57 | 1 | 115 | 55 | 1 | 112 | 58 | 1 | |||
M0 | 51 | 27 | 24 | 0.57 (0.30–1.07) | 0.081 | 27 | 24 | 0.54 (0.28–1.02) | 0.057 | 35 | 16 | 1.13 (0.58–2.22) | 0.716 |
M1 | 5 | 2 | 3 | 0.34 (0.05–2.07) | 0.240 | 2 | 3 | 0.32 (0.05–1.96) | 0.218 | 1 | 4 | 0.13 (0.01–1.19) | 0.070 |
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Jahan, N.; Begum, M.; Barek, M.A.; Aziz, M.A.; Hossen, M.S.; Bhowmik, K.K.; Akter, T.; Islam, M.R.; Abdulabbas, H.S.; Islam, M.S. Evaluation of the Association between FGFR2 Gene Polymorphisms and Breast Cancer Risk in the Bangladeshi Population. Genes 2023, 14, 819. https://doi.org/10.3390/genes14040819
Jahan N, Begum M, Barek MA, Aziz MA, Hossen MS, Bhowmik KK, Akter T, Islam MR, Abdulabbas HS, Islam MS. Evaluation of the Association between FGFR2 Gene Polymorphisms and Breast Cancer Risk in the Bangladeshi Population. Genes. 2023; 14(4):819. https://doi.org/10.3390/genes14040819
Chicago/Turabian StyleJahan, Nusrat, Mobashera Begum, Md Abdul Barek, Md. Abdul Aziz, Md. Shafiul Hossen, Khokon Kanti Bhowmik, Tahmina Akter, Md. Rabiul Islam, Hadi Sajid Abdulabbas, and Mohammad Safiqul Islam. 2023. "Evaluation of the Association between FGFR2 Gene Polymorphisms and Breast Cancer Risk in the Bangladeshi Population" Genes 14, no. 4: 819. https://doi.org/10.3390/genes14040819
APA StyleJahan, N., Begum, M., Barek, M. A., Aziz, M. A., Hossen, M. S., Bhowmik, K. K., Akter, T., Islam, M. R., Abdulabbas, H. S., & Islam, M. S. (2023). Evaluation of the Association between FGFR2 Gene Polymorphisms and Breast Cancer Risk in the Bangladeshi Population. Genes, 14(4), 819. https://doi.org/10.3390/genes14040819